Toxicology – Antidotes for Cyanide Poisoning

Indications

Cyanide poisoning should be suspected in patients with severe smoke inhalation or occupational exposure who develop findings such as:

• Altered mental status
• Dyspnea
• Seizures
• Coma
• Cardiovascular collapse
• Severe tissue hypoxia and lactic acidosis

Because confirmatory testing is often too slow to guide emergency care, treatment may need to begin based on the clinical picture.

Hydroxocobalamin

Hydroxocobalamin is generally the preferred antidote, especially in smoke-inhalation cases.

Mechanism

• Contains a cobalt atom that binds cyanide
• Forms cyanocobalamin (vitamin B12)
• The resulting compound is then eliminated by the kidneys

Advantages

• Does not induce methemoglobinemia
• Can be used when concurrent carbon monoxide poisoning is suspected
• Does not typically cause significant hypotension

Adverse Effects

• Red discoloration of the skin
• Red urine (chromaturia)
• Headache
• Nausea or vomiting
• Itching

Sodium Thiosulfate

Sodium thiosulfate provides sulfur that the enzyme rhodanese uses to convert cyanide into the much less toxic compound thiocyanate, which is eliminated through the kidneys.

It can be used in smoke-inhalation patients because it does not create methemoglobinemia.

Possible adverse effects include:

• Nausea
• Vomiting
• Hypotension

Nitrites – Amyl Nitrite and Sodium Nitrite

Nitrites convert normal hemoglobin into methemoglobin. Cyanide preferentially binds to methemoglobin rather than mitochondrial cytochrome oxidase, helping remove cyanide from its cellular target.

However, methemoglobin cannot effectively carry oxygen. For this reason, nitrites are generally avoided or used very cautiously when carbon monoxide poisoning or significant smoke inhalation is also present.

Rapid IV administration of sodium nitrite may also cause:

• Marked vasodilation
• Hypotension
• Tachycardia

Mechanism Summary

Cyanide antidotes work mainly by:

• Binding cyanide directly: hydroxocobalamin
• Enhancing detoxification to thiocyanate: sodium thiosulfate
• Creating an alternative cyanide-binding target: nitrites

Key Points

• Hydroxocobalamin is particularly useful in smoke-inhalation cyanide poisoning.
• Sodium thiosulfate assists the body’s natural cyanide-detoxifying pathway.
• Nitrites induce methemoglobinemia and may worsen oxygen delivery when carbon monoxide poisoning is also present.
• Cyanide treatment should not be delayed in a critically ill patient when the clinical suspicion is high.